Rare Developmental Brainstem Abnormality

Case Presentation

A 5-month-old baby presented with congenital right facial palsy, bilateral hearing loss and feeding difficulties. The patient was born at 36 weeks’ gestation by cesarean section with an uncomplicated delivery. The right facial weakness was present since birth. Genetic testing was negative. Additionally, echocardiogram and renal ultrasound were also normal. An electroencephalogram demonstrated epileptiform changes without seizures. Physical examination showed right facial weakness with response to touch bilaterally, diffuse increased motor tone in all extremities, and decreased truncal tone. No gross coordination abnormalities were seen. Subsequently, an MRI of the brain and internal auditory canals were performed (Figures 1-4).

Key Imaging Findings

Hypoplasia of the cerebellum and vermis

Hypoplasia of the middle cerebellar peduncles

Hypoplasia of the pons

Dorsal pontine bump

Absence of the 7th and 8th nerves

Differential Diagnosis

Joubert syndrome

Pontocerebellar hypoplasia

Pontine tegmental cap dysplasia

Discussion

Significant advancements in the prenatal and postnatal imaging techniques over recent years have improved our understanding of pediatric posterior fossa developmental abnormalities. Additionally, research in developmental biology and genetics have further helped in classification of congenital posterior fossa abnormalities. Congenital posterior fossa anomalies may be broadly divided into genetic malformations and anomalies due to disturbances during development such as infection and other processes.¹ The majority of the posterior fossa anomalies involve the cerebellum to some extent, resulting in hypoplasia or dysplasia. There are subtle differences between various posterior fossa anomalies and recognizing those differences on the initial imaging study is important in terms of identifying the correct diagnosis for patients and clinicians. Coronal T2, sagittal T1- and T2-weighted imaging, as well as balanced steady-state gradient echo sequences are helpful in diagnosing posterior fossa anomalies.

Joubert Syndrome

Joubert syndrome is an autosomal recessive disorder characterized by hypotonia, breathing abnormalities, and intellectual disabilities. The classic imaging appearance is the molar tooth sign consisting of thickened and horizontally oriented superior cerebellar peduncles, hypoplasia of the cerebellum and vermis, and a deep interpeduncular fossa.^2,3 In some variations of this syndrome, abnormalities also include dysmorphic appearance of the tectum and midbrain, hypoplasia of the pons, callosal dysgenesis, hippocampal malrotation, and migrational disorders.³ This syndrome also may be associated with several systemic disorders including renal, ocular, hepatic, and skeletal abnormalities.

Pontocerebellar Hypoplasia

Pontocerebellar hypoplasia (PCH) is a group of autosomal recessive disorders characterized by hypoplasia of the cerebellum and pons.^4,5 The typical imaging findings include hypoplasia of the cerebellum including the cerebellar hemispheres with relative preservation of the vermis, resulting in a “dragonfly” appearance.¹ The normal pontine volume is significantly decreased. Delayed myelination may be present. The morphologic pattern of pontocerebellar hypoplasia, however, has also been shown in other etiologies such as extreme prematurity and neurometabolic diseases such as glycosylation type and patients with mutations in CASK (calcium/calmodulin-dependent serine protein kinase) gene. Morphologic pattern of pontocerebellar hypoplasia can also be seen with congenital muscular dystrophies that are caused by defective dystroglycan O-glycosylation.^6,7

Pontine Tegmental Cap Dysplasia

Pontine tegmental cap dysplasia is a rare posterior fossa developmental abnormality with involvement of the vestibulocochlear, facial and trigeminal nerves, resulting in facial paralysis, and hearing loss among other abnormalities.⁸ The characteristic imaging findings for this particular entity include a flattened appearance of the ventral pons (loss of the pontine belly) with a paradoxical bump involving the tegmentum of the pons, hypoplasia of the middle cerebellar peduncles, vermian hypoplasia, and absent inferior olivary prominence. This malformation is considered sporadic with an unknown genotype and the prognosis is highly variable. Diffusion tensor imaging may demonstrate absence of posterior positioning of the transverse pontine fibers. The underlying mechanism is uncertain but has been hypothesized to be related to abnormal migration of the neurons in the pontine tegmentum.⁹

Diagnosis

Pontine tegmental cap dysplasia

Conclusion

Malformations of the brainstem result in severe clinical manifestations, including feeding disorders, hearing loss, and cranial nerve palsies. Pontine tegmental cap dysplasia is a rather recently classified malformation. Helpful imaging findings in diagnosing this condition include volume loss of the normal pontine belly with a dorsal tegmental prominence, hypoplasia of the cerebellar vermis, hypoplasia of the middle cerebellar peduncles, and absence of the 7th and 8th cranial nerves. The disorder may be more common than previously thought and knowledge of its constellation of findings can aid accurate diagnosis.

References

1. Bosemani T, Orman G, Boltshauser E, et al. Congenital abnormalities of the posterior fossa. RadioGraphics 2015;35(1):200-220.
2. Gleeson JG, Keeler LC, Parisi MA, et al. Molar tooth sign of the midbrain-hindbrain junction: occurrence in multiple distinct syndromes. Am J Med Genet A 2004;125A(2):125-134; discussion 117.
3. Poretti A, Huisman TA, Scheer I, et al. Joubert syndrome and related disorders: spectrum of neuroimaging findings in 75 patients. Am J Neuroradiol 2011;32(8):1459-1463.
4. Barth PG. Pontocerebellar hypoplasias: an overview of a group of inherited neurodegenerative disorders with fetal onset. Brain Dev 1993;15(6):411-422.
5. Namavar Y, Barth PG, Kasher PR, et al. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain 2011;134(pt 1):143-156.
6. Feraco P, Mirabelli-Badenier M, Severino M, et al. The shrunken, bright cerebellum: a characteristic MRI finding in congenital disorders of glycosylation type 1a. Am J Neuroradiol 2012;33(11):2062-2067.
7. Messerschmidt A, Brugger PC, Boltshauser E, et al. Disruption of cerebellar development: potential complication of extreme prematurity. Am J Neuroradiol 2005;26(7):1659-1667.
8. Barth PG, Majoie CB, Caan MW, et al. Pontine tegmental cap dysplasia: a novel brain malformation with a defect in axonal guidance. Brain 2007;130(pt 9):2258-2266.
9. Jissendi-Tchofo P, Doherty D, McGillivray G,. et al. Pontine tegmental cap dysplasia: MR imaging and diffusion tensor imaging features of impaired axonal navigation. Am J Neuroradiol 2009;30(1):113-119.